Blood levels of homocysteine are elevated in Alzheimer's disease (AD), and hyperhomocysteinemia may contributed to disease pathophysiology by vascular and direct neurotoxic mechanisms. Homocysteine levels can be reduced to administrating of high dose supplements of folate, vitamin B6 and vitamin B12. We propose a multicenter, randomized, controlled clinical trial to determine whether reduction of homocysteine levels with high-dose folate/B6/B12 supplementation will slow the rate of cognitive decline in subjects with AD. This will be a parallel design study, including two groups of unequal size: (60% of subjects will receive daily high dose supplements (folate 5mg, vitamin B6 50MG, vitamin B12 1 mg), and 40% will receive identically appearing placebo; the duration of treatment will be 18 months. The primary outcome measure will be longitudinal decline in the ADAScog. To power the trial to detect a 25% reduction in rate of ADAScog decline (80% power, alpha=0.05, drop-out estimate 20%, drop-in estimate 10%), we will enroll a total of 400 subjects.